Advantages of myeloid progenitors over of macrophages or neutrophils for myeloid cell therapies.

What is it about?

Myeloid progenitor cells can temporarily engraft and produce innate immune cells, like neutrophils and macrophages, inside the patient over a few weeks. This could drastically lower the cell numbers required for cell therapy and extend the duration of effect, as compared to primary macrophage or neutrophil therapies. Thus, myeloid progenitor transfusions might be superior to effector cells for many applications.

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Photo by National Cancer Institute on Unsplash

Photo by National Cancer Institute on Unsplash

Why is it important?

Chemotherapy often destroys the bone marrow, the organ system that produces our blood cells inclusing our immune cells. This especially affects our shortlived innate immune cells, like neutrophils, that make up the body's first line of defense. Thus, under chemotherapy or during bone marrow transplantation, many patients are highly vulnerable to infections because they do not have enough innate immune cells. Other than for example for red blood cells or platelets, myeloid effector cells, like neutrophils, cannot effectively be replaced by transfusions because they are so shortlived. Thus, there is currently no satisfying therapy for the lack of neutrophils (neutropenia), which affects circa 70,000 patients in the US per year with a mortality of approxamately 7% despite broad-spectrum antibiotic therapy and expensive growth-factor treatment. Transfusing myeloid progenitors, the cells taht make neutrophils and other innate immune cells, could thus bridge the vulnerable period after chemotherapy by transiently settling into a patient's body and producing neutrophils while the patient's boen marrow is not working. This has been shown to protect patients from infections and improve outcomes. In extension, this technology could help making other myeloid cell based immune therapies feasible: Myeloid cells, like neutrophils, macrophages, and dendritic cells, excel at homing to sites of inflammation in the body, attacking pathogens, and modulating the local immune response. They are thus promising to either increase immune responses, for example against tumors, or decreasing inappropriate immune responses, for example against transplant organs or in autoimmune conditions. However, like with neutrophils transfusions (above), is is very challenging to provide enough cells for such therapies. In addition, due to their shortlived nature, myeloid immune cells are difficult to bioengineer, for example to instruct them to attack a certain target, like a tumor cells. Myeloid progenitors, on the other hand, are relatively stable in culture, especially when derived from a practically unlimited source of induced pluripotent stem cells. In addition, they can be frozen, which allows for "off-the-shelf" provision. As they amplify and produce effector cells over multiple weeks inside the host's body, they could drstically reduce the cell numbers and number of repeated transfusions needed for myeloid therapies, thus making these economically feasible for large scale application.

Perspectives